This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Patients with advanced head and neck squamous cell cancer HNSCC) are difficult to treat due to their tumor burden and co-morbid conditions. Overall survival for this unfortunate group of patients has not improved, significantly, in the past 30 years. Preclinical studies have demonstrated that opiod growth factor (OGF) and its receptor, OGFr, form a tonically active growth inhibitory system that targets cell replication in HNSCC. Phase I studies in patients with unresectable pancreatic cancer has been somewhat efficacious. The safety and maximum tolerated dose of OGF, in humans, has been established and it has been approved by the FDA. The objective of this study is to determine the efficacy of the OGF-OGFr axis in the treatment of 50 patients with advanced HNSCC in terms of survival and quality of life.